Transcept Pharmaceuticals, Inc. has announced its plan for the resubmission for the Intermezzo® New Drug Application (NDA) based on a teleconference with the U.S. Food and Drug Administration (FDA) held earlier today. The key component of the resubmission plan is an Intermezzo® highway driving study to assess next day residual effects, for which Transcept now expects to begin enrollment in the late second quarter of 2010. Based on the teleconference with FDA, and pending a positive highway driving study outcome, Transcept estimates that it will resubmit the Intermezzo® NDA in the late fourth quarter of 2010.
Update on the Intermezzo® NDA resubmission plan
In the October 28, 2009 Intermezzo® Complete Response Letter, the FDA expressed two concerns regarding the possibility of middle of the night patient dosing errors that could lead to next day residual effects, with particular reference to next day driving impairment. Specifically, the FDA asked Transcept to address methods to avoid inadvertent re-dosing in a single night, and inadvertent dosing with less than four hours of bedtime remaining.
A meeting was held on January 20, 2010 to discuss the Intermezzo® Complete Response Letter, during which the FDA indicated that the Transcept proposal to employ a single unit dose package appeared to reduce the potential for inadvertently taking more than one Intermezzo® dose in a single night.
During the March 24, 2010 teleconference, the FDA agreed that the Transcept proposal submitted on February 16, 2010 to conduct a highway driving study is a reasonable way to measure potential next day driving impairment as a result of dosing Intermezzo® in the middle of the night with four hours or less remaining in bed. This study will be conducted at the University of Maastricht in the Netherlands, a leading center of research on the effects of drugs and alcohol on driving performance.
Key elements of the highway driving study include:
-- Approximately 36 adult subjects
-- Highway driving over a one-hour perio
-- Single center, double-blind, randomized, placebo-controlled crossover design
-- Key comparisons:
-- Intermezzo® 3.5mg vs. placebo, 4 hours post-dose
-- Intermezzo® 3.5mg vs. placebo, 3 hours post-dose
-- Zopiclone 7.5mg vs. placebo (positive control)
-- Primary endpoint: deviation of lateral position as compared to placebo
In earlier interactions, the FDA and Transcept discussed whether a patient use study might help to define patient ability to properly follow instructions under actual conditions of use. During the March 24, 2010 teleconference, the FDA indicated that, during the review of the overall resubmission of the Intermezzo® NDA, it would consider the Transcept position regarding the challenges and limitations of a pre-approval patient use study. Transcept also plans to include data from on-going studies of patient comprehension of label instructions in this resubmission.